1. Technical Field
The present invention relates to small-volume liquid dispensing technology, and more particularly to technology that uses acoustic energy to cause droplets of the liquid to be dispensed.
2. Background Information
Many methods for precision transfer and handling of liquids are known and used in a variety of commercial and industrial applications. A common method for high throughput precision liquid transfer is contact printing/deposition. However, contact printing requires the direct contact of a transfer device with the target surface, thus increasing the risk of contaminating the source liquid and/or its deposition interface. Cross-contamination is particularly problematic for biotechnology and biopharmaceuticals processes where ultrapure liquid handling and transfer techniques are required. Not only is purity a concern, current biotechnological screening and manufacturing methods also require high throughput to efficiently conduct screening of compound libraries, synthesis of screening components, and other similar biochemical processes.
Liquid transfer methods that require contacting the target surface not only increase the likelihood of contamination, but also decrease the rate of liquid transfer. Because precision contact needs to be achieved between the print-head and the target surface, elaborate mechanical controls and/or cleaning mechanisms are usually required. This complex machinery may not conveniently and reliably produce high-density arrays. For example, in the manufacturing of high density microarrays, a sophisticated mechanical system would be required to control the print-head for contact with the target surface in the printing process. The mechanical movement of the print head to and from the target surface may increase liquid transfer time and limit system accuracy. The precision mechanical parts that are necessary to support movement of the print head may also increase system failure rate. Many biotechnology procedures require high throughput precision transfer of liquid, and have low tolerances for contaminations. Accordingly, a noncontact method for liquid transfer may be desirable.
Various non-contact printing/deposition techniques have been previously developed to overcome the limitation of contact printing techniques. Two common approaches are piezoelectric printing and syringe-solenoid printing. Piezoelectric printing may lead to the capturing of air bubbles in the output droplet. In addition, the droplet size is dependent on the size of the orifice. Thus, to generate microliter droplets, the size of the output orifice would typically be in the micron range. An output nozzle with a small orifice is susceptible to clogging. In addition, one may need to replace the nozzle in order to modify the droplet output size. In applications where multiple source liquids are being utilized, changing the source liquid may require replacement of the complete print-head, since typically the piezoelectric crystals are bonded with the output nozzle.
In a typical syringe-solenoid printing device, an electrically controlled mechanical valve is required to manage the liquid droplet output. This may result in large droplet size and slow liquid droplet ejection rate. In addition, a mechanical valve may be more prone to clogging and mechanical failure. In contrast, a liquid deposition apparatus that does not have a mechanically moving component in the liquid container may be more reliable.
Biotechnology screening techniques may involve many thousands of separate screening operations, with the concomitant need for many thousands of liquid transfer operations in which small volumes of liquid are transferred from a liquid source to multiple target sites. Similarly, biotechnology synthesis methods for the generation of tools useful for conducting molecular biology research often require many iterations of a procedure that must be conducted without contamination and with precision. Thus, a non-contact liquid transfer technique that allows precision transfer of liquids at high rate is desirable. In addition, a liquid transfer apparatus that allows the operator to control/modify the volume of liquid during the transferred procedure without changing or moving mechanical parts may provide various added advantages.
In order to meet these needs, methods have been developed utilizing acoustic waves to eject liquids out of source reservoirs. The acoustic droplet ejection systems allow for a non-contact method for the precision-transfer of small amounts of liquid in a rapid manner that is easily automated to meet industry needs. For example, U.S. Pat. No. 6,596,239, titled “ACOUSTICALLY MEDIATED FLUID TRANSFER METHODS AND USES THEREOF” issued to Williams et al., dated Jul. 22, 2003, is representative of the prior art. However, most of the prior art devices are configured to eject liquid in an upward direction. In various biological/chemical applications it is desirable to transfer liquid in a downward direction. For example, as mentioned earlier, to synthesize high density micro-array on a substrate, it may be desirable to deposit biologics or chemicals in a top down fashion.
Thus, an acoustic liquid deposition apparatus that is capable of transferring precision liquid droplets at a high rate is desirable. Preferably the apparatus may be adapted to eject liquid droplets in various directions and angles. It may also be desirable to adapt the apparatus to support on-the-fly modification of ejected liquid volume. Furthermore, for biological/chemical synthesis or screening applications, a built-in capability to characterize the physical parameters (e.g., concentration, density, viscosity, etc.) of the source liquid to be ejected may be particularly valuable.